Many neurological disorders are presently incurable, but are treatable with medications that alleviate symptoms and/or improve cognitive function. One of the principal neurological disorders, independent of age, is epilepsy. Over 10% of the population will experience at least one seizure. However, the prevalence of epilepsy does vary with age, and is high during infancy, diminishes during childhood; reaches a nadir during both adolescence and adulthood, and then goes up significantly in old age. Epileptics are characterized by the incidence of seizures, although seizures also occur in other neurological disorders, and even in the absence of a disorder. Seizures are induced by transient, paroxysmal, and synchronous neuronal discharges. How a seizure manifests itself will depend on the locus and quantity of neurons involved, as well as how long a seizure discharge lasts. Willmore, J. and Wheless, J. Scientific American Medicine, sect. 11, chp 12, www.samed.com.
In contrast to the isolated seizure, epilepsy may be defined as reoccurring seizures and may be genetic or environmental in origin. Based on clinical and electroencephalographic criteria, the International League Against Epilepsy developed a widely accepted classification scheme for epilepsy, which divides seizures into three major categories: partial, generalized, and unclassified. In addition to the epilepsy classification, there is also a classification of “epilepsy syndromes”: benign childhood epilepsy with centrotemporal spikes, childhood absence epilepsy, juvenile myoclonic epilepsy, chronic progressive epilepsia partialis continua, and severe myoclonic epilepsy of childhood.
Drug therapy is the most common seizure treatment. Although antiseizure medications, known as antiepileptic drugs (AED) or anticonvulsants, had been available earlier, the introduction of phenobarbital in the early twentieth century issued in the modern era of AEDs. Willmore, J. and Wheless, J. Scientific American Medicine, sect. 11, chp 12, www.samed.com. While most AEDs were introduced before 1980, several new drugs have been recently licensed for use in epilepsy, and additional drugs in the pipeline are destined for approval in the coming years. Nevertheless there is a continuing need for new AEDs and epileptic therapies since existing therapies are not always effective or effective as they need to be.
Epileptic seizures can occur in a wide variety of disorders including the autistic spectrum disorders, also known as pervasive developmental disorders. Autistic spectrum disorders (ASD), including, but not limited to Autistic Disorder (autism), pervasive developmental delay not otherwise specified, Rhett's disorder, childhood disintegrative disorder, and Asperger's syndrome (see American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78), are long term, developmental disorders with no known or agreed upon nervous system pathology or definitive genetic site. Rodier, P. M, J. et al., Comparative Neurology 1996; 370:247-261; Bachevalier, J., Neuropsychology 1994; 32:627-648. Unfortunately, very few double-blind studies have been performed involving ASD, due to the different degrees of presentation and the multiple phenotypes of the disease. The varying symptoms observed within the ASD syndrome indicate more than a single region of injury that results in an assortment of behaviors. Rodier, P. M, J. et al., Comparative Neurology 1996; 370:247-261. With no available cure, existing treatments are directed to modifying the course of the disease.
Pervasive developmental disorders are characterized by severe and pervasive impairment in several areas of development, reciprocal social interaction skills, communication skills, or the presence of stereotyped behavior, interests and activities. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78. The principal criteria of autism include significantly abnormal or impaired development in social interaction and communication and a significantly restricted repertoire of activity and interests. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78. Depending on the developmental level and chronological age of the individual, how the disorder manifests itself can be very different.
Autism or autistic disorder is the most well known of the spectrum disorders, and is also known as early infantile autism, childhood autism and Kanner's autism. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78. Research in the past several years has shown an association between sleep electroencephalograms (EEGs) and autism. Tuchman, R., et al. CNS Spectrums 1998; 3:61-X; Deykin, E. Y. and MacMahon, B., Am. J. Psychiatry 1979; 136:1310-1312; Lewine, J. D. et al. Pediatrics 1999; 104:405-418; Tuchman, R. F. and Rapin, I. Pediatrics 1997; 99:560-566; Tuchman, R. F. et al., Pediatrics 1991; 88:1219-1225.
One-third of autistic children suffer one or more seizures by adolescence, perhaps linking epileptiform activity with some instances of ASD. Lewine, J. D. et al. Pediatrics 1999; 104:405-418. Magnetoencephalographic data has suggested that the percentage may even be higher; in a recent autistic study, 14% more children were identified as having epileptiform activity by MEG (82%) that were not identified by concurrent EEGs (68%). For more on diagnosis and testing of autism, see Barthelemy, C. et al., Brain Dysfunct. 3:271-84 (1990); American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78., and Gillberg, C., Brain Dysfunct 3:249-60 (1990).
An approach that treats the symptoms and potentially the causes of autism is the individualized nutrient therapy for autism, such as that reported in Isaacson et al., Journal of Applied Nutrition, 48, 110-118 (1996), the Autism Research Publication “Patient Ratings of Behavioral Effects of Drugs, Nutrients, and Diets”, ARI Publ. 34, Autism Research Institute, 4182 Adams Avenue, San Diego, Calif. 92116, September 2000, as well as in other references. This individualized therapy relies on treatment optimized for the individual's particular chemical imbalance, with particular nutrients emphasized in certain imbalances, and others avoided. Such individualized therapy is expensive, and a need exists for effective, cost-effective therapies for autism.
Attention Deficit and Disruptive Behavior Disorders constitute another, but related set of neurological disorders. Attention Deficit Disorder (ADD) also known as Attention Deficit Hyperactive Disorder (ADHD) is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity that is both more frequent and more severe than what is typically observed in individuals of a comparable developmental stage. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78. The inattention may be manifest in academic, occupational, or social situations. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., American Psychiatric Association, Washington, 1993, pp. 65-78.
Improved treatments are also needed for Cerebral palsy (CP). CP syndromes are a group of related motor disorders originating usually from either developmental abnormalities or perinatal or postnatal central nervous system (CNS) disorder damage occurring before 5 years of age. CP is characterized by impaired voluntary movement. While the term CP is not itself a diagnosis, the term does provide a useful classification of individuals who may suffer from nonprogressive spasticity, ataxia, or involuntary movements. Approximately a quarter of individuals with CP experience convulsive seizures. The Merck Manual, Merck Research Laboratories, 16th ed. 1992.
Improved treatments are also needed for Tourette's (Gilles de la Tourette's) Syndrome. Tourette's Syndrome comprises both multiple motor and one or more vocal tics, occurring over a period of at least one year, at least intermittently, but sometimes as frequently as many times daily. Obsessions, compulsions, hyperactivity, distractability, and impulsivity are often associated. Onset is in childhood, and tics often lessen in severity and frequency and may even remit during adolescence and adulthood. Dorland's Illustrated Medical Dictionary, 29th ed., W.B. Saunders Co., 2000.
Improved treatments are also needed for apraxias. Apraxias are defined by the inability to execute purposeful learned motor acts, even though the patient has the physical ability and willingness to perform the relevant act. Apraxias are commonly found in many metabolic and structural diseases that involve the brain diffusely, particularly those that seem to impair frontal lobe function. In a typical case, a patient cannot follow a motor command even though he or she understand it and can perform individual components of the command. The defect appears to be caused by a lesion in the neural pathways that retain memories of learned movement patterns, resulting in an inability to conceptualize necessary patterns in order to perform actions. The Merck Manual, Merck Research Laboratories, 16th ed. 1992. Specific apraxias include, but are not limited to, motor and speech apraxias. Motor or innervatory apraxia are characterized by impairment of skilled movements that is greater than different in form from that caused by weakness of the affected parts with the patient appearing clumsy rather than weak. Dorland's Illustrated Medical Dictionary, 29th ed., W.B. Saunders Co., 2000. Speech apraxia is caused by apraxia of mouth and neck muscles due to a lesion interfering with coordination of impulses from Broca's region. Dorland's Illustrated Medical Dictionary, 29th ed, W.B. Saunders Co., 2000.
Improved treatments are also needed for central auditory processing disorders. Central auditory processing disorders are characterized by hearing difficulties due to fundamental deficiencies in cognitive processing as well as to deficits in auditory perceptual processes. http://www.lindamoodbell.com/definitions/centralauditory.htm
Improved treatments are also needed for bipolar disorder (bipolar mood disorder). Bipolar disorder usually begins with depression, and includes at least one period of elation. The Merck Manual, Merck Research Laboratories, 16th ed. 1992.
Improved treatments are also needed for panic disorders (anxiety neurosis, generalized anxiety disorder and anxiety reaction). Panic disorders are characterized by chronic, unrealistic anxiety often punctuated by acute attacks of anxiety or panic. Attacks associated with panic disorders can occur repeatedly over a period of time, with durations of anywhere between a few minutes to an hour or two. The Merck Manual, Merck Research Laboratories, 16th ed. 1992.
Improved treatments are also needed for dyslexia. While there is no universally accepted definition or set of diagnostic criteria for dyslexia, the condition can be defined generally as a condition that interferes with learning to read even though an individual has average or above-average intelligence, adequate motivation and educational opportunities, socioeconomic advantage, and normal sensory acuity. The Merck Manual, Merck Research Laboratories, 16th ed. 1992.
Improved treatments are also needed for Down's Syndrome. Down's syndrome is a trisomy resulting from an extra full or partial copy of chromosome twenty-one. Diagnosis and characterization of Down's syndrome is well known in the art.
The aforementioned conditions remain some of the least understood and difficult to treat diseases and disorders, especially amongst those conditions that afflict children. There has been a long felt need for improved therapies for all of these neurological conditions.